The proposed R00 research will be conducted at the University of Texas at Austin, and is an extension of a mentored K99 research on a Pathway to Independence Award. The objective of this research is to investigate new experimental techniques to improve the control of fear directly in anxiety pathologies. Anxiety pathologies are the most common mental illness, with a 12-month prevalence estimate of about 40 million American adults. Theoretical and technical aspects of fear conditioning continue to provide a valuable model to characterize and understand the etiology, maintenance, and treatment for pathologies of fear and anxiety. An example in the treatment domain is exposure therapy, which is based on the principles of extinction. However, prominent learning theory models have long recognized the shortcomings of extinction as a therapeutic tool; extinction is a fragile form of learning that fails to generalize, and fear behaviors tend to return over time. Clinical research in the past two decades has revealed serious deficits in the ability to control fear expression following extinction across anxiety disorder categories, including posttraumatic stress disorder, panic disorder, and phobias. Laboratory research on the limits to extinction can describe why many severe fears and anxieties relapse following clinical treatment. Accordingly, there is strong motivation to develop innovative behavioral techniques to improve the control of fear so that maladaptive fears and anxieties are more responsive to treatment and less prone to relapse. Yet, systematic neurobehavioral research on novel techniques to improve the control of fear in humans has received limited attention. During the mentored phase of this award conducted at New York University, the candidate incorporated new training on theoretical, technical, and empirical aspects of fear extinction to test new behavioral techniques to improve the control of fear in healthy adults using combination functional magnetic resonance imaging and psychophysiology methods. Aim 1 looked to override maladaptive threat associations by introducing surprising, novel, non-threat associations to the participant. Aim 2 looked to promote the generalizability of extinction learning by conducting extinction under multiple different virtual reality contexts. The R00 project will carry forward this knowledge to investigate these two new experimental tasks in clinical anxiety populations characterized by the inability to control fear expression following standard extinction procedures. Research in clinical populations was fostered by new supervised training in clinical research developed during the mentored phase. The research proposed here has the potential to advance biological models of psychopathology, establish neurobehavioral risk/resilience factors for disorders of fear and anxiety, and ultimately contribute to innovative and more effective therapeutic interventions for pathological anxiety.